Fibrosis quística en niños y su seguimiento durante 40 años 1977-2017) / Cystic Fibrosis in children and its follow up during 40 years (1977-2017)

Introducción: Los enfermos de fibrosis quística tienen mayor supervivencia y calidad de vida en las últimas décadas, debido fundamentalmente a un diagnóstico precoz. Objetivo: Describir las características de los pacientes con fibrosis quística y el seguimiento de los vivos durante 40 años. Métodos: Estudio descriptivo longitudinal retrospectivo en 96 pacientes diagnosticados con fibrosis quística en el Hospital Pediátrico Universitario William Soler (1977-2017). Los datos se obtuvieron de las historias clínicas. Se analizaron variables demográficas, temporales, clínicas, genéticas y microbiológicas. Resultados: De la muestra, actualmente se mantienen con seguimiento 27, mayores de 19 años enviados a consulta de neumología 9, fallecieron 30, no se siguen en el centro 30. El 60,4 por ciento se diagnosticó antes del primer año de vida, predominó el sexo masculino 62,5 por ciento y el color de la piel blanco 88,5 por ciento. Sugirió el diagnóstico la forma clínica respiratoria 39,6 por ciento, mixta 38,5 por ciento, digestiva 19,8 por ciento y perdedora de sal 2,1 por ciento. De los 27 casos seguidos actualmente 74,1 por ciento son eutróficos y no hay desnutridos. En el primer aislamiento microbiológico predominó la Pseudomona aeruginosa en el menor de 1 año y el Staphilococcus aureus entre 1 y 4 años. Más del 37.0 por ciento tuvo complicaciones respiratorias, el 14,8 por ciento hepática y el 40,7 por ciento sin complicaciones. La caracterización genética fue mayormente ∆F508 (70,3 por ciento). Conclusiones: Es frecuente el aislamiento de Pseudomona aeruginosa en el menor de 1 año. Casi la mitad de los pacientes no tienen complicaciones, se consiguió mejorar el estado nutricional y disminuir la mortalidad(AU)

Introduction: Patients with cystic fibrosis have had a greater survival and life quality in the last decades; this is due to a precocious diagnostic, a better nutrition state, and diminution of respiratory infections. Objective: To describe the characteristics of cystic fibrosis patients and follow up process to survivors for the last 40 years. Methods: Descriptive, longitudinal and retrospective study in 96 patients diagnosed with cystic fibrosis in William Soler Pediatric University Hospital (1977-2017). Data was obtained from clinical records. Demographic, temporary, clinical, genetic and microbiological variables were analized. Results: From the sample, 27 patients keep under medical follow up; 9 patients older than 19 years old were remitted to the Neumology consultation; 30 died; and 30 patients are not followed up at the hospital. 60.4 percent of the patients was diagnosed before the first year of life, t was predominant the male sex (62.5 percent) and most of them were white skin (88.5 percent). Diagnosis suggested; the respiratory clinical symptoms, 39.6 percent; mixed, 38.5 percent; digestive symptoms, 19.8 percent; salt lost, 2.1 percent. Out of the 27 cases followed at present, 74.1 percent are eutrophics, and there are not patients with malnutrition. In the first microbiological isolation, Pseudomonas aeruginosa prevailed in patients under 1-year-old and Staphilococcus aureus in patients between 1 and 4 years old. More than 37.0 percent of patients had respiratory complications, 14.8 percent had hepatic complications, and 40.7 percent had no complications. The genetic characterization was mostly of ∆F508 (59.2 percent). Conclusions: Pseudomonas aeruginosa is frequently in patients under 1-year-old. Almost half of the patients has no complications; and it is improved their nutritional state and mortality decreased(AU)

Sweat test and cystic fibrosis: overview of test performance at public and private centers in the state of São Paulo, Brazil / Teste do suor e fibrose cística: panorama da realização do teste em centros públicos e privados do estado de São Paulo

ABSTRACT Objective: The sweat test (ST) measures chloride levels in sweat and is considered the gold standard for the diagnosis of cystic fibrosis (CF). However, the reliability of a ST depends on their being performed by experienced technicians and in accordance with strict guidelines. Our aim was to evaluate how sweat stimulation, sweat collection, and chloride measurement are performed at 14 centers (9 public centers and 5 private centers) that routinely perform STs in the state of São Paulo, which has the highest frequency of CF in Brazil. Methods: This was a cross-sectional cohort study, using a standardized questionnaire administered in loco to the staff responsible for conducting STs. Results: No uniformity regarding the procedures was found among the centers. Most centers were noncompliant with the international guidelines, especially regarding the collection of sweat (the samples were insufficient in 10-50% of the subjects tested); availability of stimulation equipment (which was limited at 2 centers); modernity and certification of stimulation equipment (most of the equipment having been used for 3-23 years); and written protocols (which were lacking at 12 centers). Knowledge of ST guidelines was evaluated at only 1 center. Conclusions: Our results show that STs largely deviate from internationally accepted guidelines at the participating centers. Therefore, there is an urgent need for standardization of STs, training of qualified personnel, and acquisition/certification of suitable equipment. These are essential conditions for a reliable diagnosis of CF, especially with the increasing demand due to newborn screening nationwide, and for the assessment of a possible clinical benefit from the use of modulator drugs.

RESUMO Objetivo: O teste do suor (TS) mede os níveis de cloro no suor e é considerado o padrão ouro para o diagnóstico da fibrose cística (FC). Contudo, a confiabilidade do TS depende de sua realização por técnicos experientes e segundo diretrizes rígidas. Nosso objetivo foi avaliar como são realizadas a estimulação e coleta do suor e a dosagem de cloro em 14 centros (9 públicos e 5 privados) que realizam TS rotineiramente no estado de São Paulo, que possui a maior frequência de FC do Brasil. Métodos: Estudo de coorte transversal utilizando um questionário padronizado aplicado in loco ao pessoal responsável pela realização dos TS. Resultados: Não houve uniformidade entre os centros quanto aos procedimentos. A maioria dos centros não era aderente às diretrizes internacionais, especialmente quanto à coleta do suor (amostras insuficientes em 10-50% dos indivíduos testados), disponibilidade de equipamentos de estimulação (limitada em 2 centros), modernidade e certificação dos mesmos (a maioria utilizada há 3-23 anos) e protocolos escritos (ausentes em 12 centros). Avaliou-se o conhecimento sobre diretrizes para TS em apenas 1 centro. Conclusões: Nossos resultados mostram que, nos centros participantes, os TS estão muito distantes das diretrizes internacionalmente aceitas. Portanto, há necessidade urgente de padronização dos TS, de treinamento de pessoal qualificado e de aquisição/certificação de equipamentos adequados. Essas são condições essenciais para um diagnóstico confiável de FC, especialmente com a crescente demanda resultante da triagem neonatal em todo o país, e para a avaliação do possível benefício clínico do uso de moduladores.

Deficiencia de vitamina A en niños con fibrosis quística / Vitamin A deficiency in children with cystic fibrosis

INTRODUCCIÓN: la carencia subclínica de vitamina A es frecuente en niños y adolescentes con fibrosis quística, y tiene un origen multifactorial; contribuye al deterioro pulmonar y ensombrece el pronóstico de la enfermedad. OBJETIVO: caracterizar el estado de esta vitamina en niños y adolescentes fibroquísticos y su relación con el estado nutricional y algunas variables clínicas. MÉTODOS: se realizó un estudio descriptivo, transversal (año 2014), de los 11 pacientes menores de 18 años atendidos en consulta multidisciplinaria del Hospital Pediátrico Centro Habana, que recibían suplementos diarios de vitamina A, como parte de la recomendación dietética y que se encontraban estables de su enfermedad, sin síntomas carenciales. Se evaluó el nivel de retinol sérico por cromatografía de alta resolución y se consideraron valores normales, según la OMS, entre 30 y 79 µg/dL, marginales entre 20 y < 30 µg/dL y deficiencia subclínica entre 10 y < 20 µg/dL. El estado nutricional se evaluó según percentil de índice de masa corporal, correspondiente a la población cubana según edad decimal y sexo. Se clasificó, además, a los enfermos, según mutación reportada, presencia de insuficiencia pancreática y enfermedad pulmonar típica, de acuerdo con registros clínicos. RESULTADOS: en la muestra predominó la mutación del 508F (2 homocigotos y 6 heterocigotos) y la enfermedad típica con insuficiencia pancreática (10 de 11). En 7 niños (63,6 %) se detectaron niveles bajos de vitamina A (4 marginales y 3 deficientes), con predominio en niños con bajo peso (80 vs. 50 % en los eutróficos), prescolares (2 de 2) y adolescentes (3 de 5). CONCLUSIONES: es importante el monitoreo de esta vitamina en el seguimiento de los enfermos de fibrosis quística.

INTRODUCTION: subclinical Vitamin A deficiency is common in children and adolescents with cystic fibrosis of multifactoral origin; it influences the pulmonary deterioration and casts a shadow over the disease prognosis. OBJECTIVE: to characterize the state of this vitamin in children and adolescents with cystic fibrosis and its association with the nutritional status and with some clinical variables. METHODS: a cross-sectional and descriptive study was conducted in younger than 18 years-old children. They were seen at the multidisciplinary service of Centro Habana pediatric hospital, and received daily Vitamin A supplements as part of dietary recommendations; they were stable with no symptoms of shortage at the time of study. A high resolution chromatography evaluated the level of serum retinol, whose values, according to WHO standards, were considered normal when yielding 30-79 µg/dL, marginal from 20 to less than 30 µg/dL and subclinical deficiency ranging from 10 to lower than 20 µg/dL. The nutritional status was measured as body mass index percentiles of the Cuban population by decimal age and sex. Additionally, the patients were classified on the basis of reported mutation, pancreatic deficiency and typical pulmonary disease pursuant to the medical histories. RESULTS: in the sample, the 508F mutation (2 homozygotic and 6 heterozygotic) and typical disease with pancreatic disease (10) prevailed. Seven children (63.2 %) had low Vitamin A levels (4 marginal and 3 deficient), being low weighed children (80 vs. 50 % in the eutrophic ones), preschool children (2 out of 2) and adolescents (3 out of 5) predominant. CONCLUSIONS: it is important to monitor Vitamin A in the follow-up of patients with cystic fibrosis.

Guía de Práctica Clínica para la prevención, diagnóstico, tratamiento y rehabilitación de Fibrosis Quística / Clinical Practice Guideline for prevention, diagnosis, treatment and Cystic Fibrosis rehabilitation

Determinar los criterios y las técnicas de diagnóstico adecuadas para la detercción temprana de la enfermedad. Proporcionar las recomendaciones para la correcta referencia del paciente con sospecha o con la enfermedad. Definir los estándares mínimos de diagnóstico y tratamiento requeridos para la atención de los pacientes con FQ.

O conhecimento do profissional de saúde frente à fibrose cística / Knowledge of the health professional about cystic fibrosis

Trata-se de uma pesquisa que objetivou investigar o conhecimento dos profissionais da área de saúde diante de patologias que apresentam sintomatologia similar a outras, como é o caso da fibrose cística. Doença autossômica recessiva acomete principalmente caucasianos, causando inúmeras mutações que desorganizam o transporte epitelial de cloro, aumentando sua concentração no suor. Os sujeitos pesquisados foram dez profissionais de saúde e os resultados demonstraram que, apesar dos sujeitos apresentarem conhecimento teórico, demonstrou dúvidas nas técnicas para o diagnóstico precoce.

Nutrición en el niño con fibrosis quística / Nutrition in children with cystic fibrosis

La fibrosis quística (FQ), es la enfermedad hereditaria más frecuente en la raza blanca. Uno de los objetivos de la intervención nutricional, es lograr el crecimiento y desarrollo adecuados para la edad. Dentro de las funciones del nutricionista, está reflejar investigación reciente, guías clínicas y consensos actualizados. Las técnicas antropométricas para la evaluación del niño con FQ ya están descritas en la literatura. Se considera una situación de prevención, los primeros 12 meses después de haberse realizado el diagnóstico de FQ. Varios son los factores de alarma, entre los que se encuentra el no aumento el peso. En la consulta nutricional se debe evaluar el estado de nutrición de forma periódica para detectar precozmente cambios en su estado y establecer las medidas de prevención y terapéuticas adecuadas.

Cystic fibrosis (CF) is the mot common inherited disease among caucasians. One of the goals of nutritional intervention is to achieve growth and ageappropriate development. The functions of the nutritionist is to reflect recent research, current clinical guidelines and consensus. Anthropometric techniques for the evaluation of children with CF are described in the literatura. It is considered a prevention situation, the first 12 months after the diagnosis of CF.

Screening for cystic fibrosis: the importance of using the correct tools

Cystic Fibrosis [CF] is a potentially lethal genetic disorder. The most frequent mutation worldwide in the Cystic Fibrosis Transmembrane Conductance Regulator [CFTR] gene is designated as the Delta F508 mutation. This mutation was found in only 33% of Pakistani patients studied. Since the common Pakistani mutations remain to be identified, appropriate screening tools are required to identify disease. Sweat chloride determinations remain the gold standard for diagnosing CF. This study was done to emphasize the importance of using the correct tests. The study was conducted at the Aga Khan University Hospital. The CFTR delta F508 mutation was tested on blood samples from patients suspected with CF. Sweat chloride analysis using pilocarpine iontopharesis was done with a positive value of greater than 60 meq/L. 57 pediatric samples were screened for the delta F508 mutation and were positive in only 10.6% of all patients tested. 12/57 [21%] had a preliminary sweat test. 6/12 [50%] of these patients had an abnormal sweat test and 3/6 patients with an abnormal sweat chloride [50%] had deltaF508 mutations - 2/6 [33%] were homozygotes and 1 was a compound heterozygote. Since 79% did not have a sweat test, it was difficult to assess whether this subset of patients had cystic fibrosis with a CFTR mutation other than the delta F508 tested or no CF. Sweat chloride analysis is critical to distinguish CF from other causes of severe pulmonary and pancreatic insufficiencies and to define patients requiring further analysis

Modern trends in the biomedical sciences

This work presents some aspects of modern biomedical science that particularly contribute to its application to conquer disease. Two examples are used to show developments in methodology may contribute toward this end .The knowledge about the mechanisms of disease in the case of cholera on the one hand, and of cystic fibrosis, on the other, are leading to new possibilities of prevention and treatment of these diseases. In both cases, membrane transport defects are the underlying cause of their pathology. The nature of these defects has been investigated by in vivo and in vitro studies of ion transfer across the involved epithelia (intestinal and airway), including electrophysiological and single channel studies. The nature of the involved membrane transporters (in cystic fibrosis) as well as of the toxins that cause the symptoms of cholera has been determined by molecular biology methods, which have also detected the genetic defects responsible for the anomalous transporters. In addition, the genes responsible for the production of different main and accessory cholera enterotoxins have been defined, allowing the elaboration of vaccines that may prevent the effect of infection by Vibrio cholerae.This new knowledge may lead, in the future, to improved ways to detect, treat and prevent these and other diseases.

Fibrosis quística: enfoque prenatal / Cystic fibrosis: pre-natal diagnosis

Se presentan casos clínicos reiterativos en recién nacidos con fibrosis quística; hijos de cónyuges ambos heterozigotos portadores de la enfermedad. Se describen los progresos diagnósticos de esta afección genética y su prevención

Fibrosis quística en niños mexicanos: análisis de 39 casos diagnosticados en vida / Cystic fibrosis in mexican children: analysis of 39 cases diagnosed in alive patients

La fibrosis quística (FQ) en México ha sido considerada, hasta años recientes, como una enfermedad inexistente o poco frecuente. En realidad no se conoce su frecuencia en la población general. A nivel institucional la frecuencia de FQ es de 1% en el material de autopsias. Los autores atribuyen su excepcional identificación a la falta de conocimientos de la enfermedad, a la patología intercurrente relacionada con el medio y a la temprana mortalidad de los niños afectados. Sobre estas bases se justifica esta publicación, cuyo objetivo es difundir el perfil clínico de la FQ en nuestro medio, los criterios diagnósticados y las perspectivas en su prevención y tratamiento. Se analizaron 39 casos diagnosticados en vida entre 1981 y 1988. El diagnóstico se estableció en presencia de un cuadro clínico sugestivo y cifras de cloro en sudor de 60 o más mEq/L (mmol/L). El cuadro clínico fué similar al que ha sido descrito en la población de los países desarrollados; sin embargo, se encontraron diferencias importantes en relación con la severidad del daño y con la pobre esperanza de vida observados en esta serie. La desnutrición primaria y la diarrea crónica, que son frecuentes en nuestro medio, constituyeron un importante distractor clínico. La agudización de la afección respiratoria crónica fue la principal causa de muerte a una edad promedio de cuatro años. Se menciona que actualmente es posible establecer el diagnóstico pre-natal de FQ, midiendo los niveles de alfa-glutamil-transpeptidasa y otras enzimas que se producen en las vellosidades intestinales del embrión y que se encuentran disminuidas en el líquido amniótico en casos de FQ; también es posible identificar a los portadores sanos mediante técnicas de ingeniería genética que ubican al locus de la FQ y a los marcadores de DNA que se relacionan con este locus, en el cromosoma 7. La aplicación de estas técnicas en la clínica permitirá, tal vez, evitar la procreación entre portadores sanos cuyo riesgo es tener hijos enfermos de FQ es de 25% en cada embarazo.

Açöes específicas da equipe multiprofissional na assistência a crianças portadoras de mucoviscidose: I - Controle de Natalidade / Specific actions of the multiprofessional team in the care of children with mucoviscidosis: I - Birth control

No planejamento familiar em famílias de crianças portadoras de mucoviscidose, estuda-se a importância da própria doença como fator determinante do planejamento. Apresentam-se e discutem-se as expectativas de uma populaçäo de crianças mucoviscidóticas matriculadas na Unidade de Pneumologia do Instituto da Criança "Prof. Pedro de Alcantara" com relaçäo ao atendimento prestado pela equipe multiprofissional no que se refere ao planejamento familiar